Atypical femoral fractures (AFF) of the subtrochanteric region are rare. Bisphosphonates account to a large extent to their occurrence, however AFF also occur without exposure to bone medication. We here assessed the genetic factors associated with AFF among subtrochanteric fractures. Cases of subtrochanteric or femoral shaft fractures were identified through ICD-10 codes in three French academic centers from 2007 to 2010. Medical records were analyzed by two investigators that adjudicated X-rays for typical or atypical fractures. Among them, genetic screening for ALPL or COLA1/A2 variants was performed after patients information and consent. A total of 389 cases were identified and 268 were ruled out. On the remaining 121, 14 (11.6%) patients had AFF. No clinical characteristic differed between groups. In the AFF group, four were exposed to bisphosphonates and one to raloxifene. Genetic analysis was could be performed in five patients and found one patient with a heterozygous mutation in COL1A2 gene (NM_000089.3:c.2123G, rs72658163, p.Arg708Gln) and three patients with various heterozygous ALPL mutations of unknown significance. This mutation in COL1A2 has been previously described in a patient with atypical Marfan syndrome. Our patient was 78-year-old and did not show any sign of Marfan syndrome. She had been treated more than 5 years by risedronate. In sillico analyses were performed showing that this variant is found in less than 0.1% of the population and is predicted to be probably damaging with a score of 1.000 and previous studies on this variant show that it does impact collagen fibril assembly and may therefore have a role as a modifier in disease pathogenesis. In conclusion, although the use of bisphosphonates is a major contributor to subtrochanteric femoral fractures. Genetic variants in COL1A2 genes was found in one out of five patients and could be a genetic background involved in this event.
14 May 2016 - 17 May 2016